Helix BioPharma Corp. New Directions in Cancer Therapies

Transcription

1 Helix BioPharma Corp. New Directions in Cancer Therapies

2 Introduction Helix is a Canadian based biopharmaceutical company developing new drugs to treat cancer, using its platform pharmaceutical technologies Million shares outstanding Traded on the Toronto Stock Exchange; symbol HBP Traded on Frankfurt Exchange; symbol HBP.F Large European shareholder base Technology covered under extensive patent base 11 Issued US; 32 issued worldwide; 3 applications

3 Helix at a Glance Management Rob Verhagen, CEO Over 20 years in biotech and life sciences management Senior executive positions with Spectral Diagnostics Inc., MDS Inc., Synsorb Biotech, Protana Denmark. Heman Chao, CSO Over 20 years in life sciences research. Former President of Sensium Technologies and senior positions with Protein Engineering Centres of Excellence (PENCE). Frank Michalargias, CFO 20 years Finance Administration experience in public and private companies including Unilever, Huhtamaki Oyi, and Trailmobile Steve Demas, Dir. of Clinical Ops Over 22 years in clinical trials management. Past experience includes clinical trial management for Spectral Diagnostics, BioMS, Bayer, and Sanofi

4 Treatment Concept

5 Tumour Microenvironment Tumours consist of a heterogenous mixture of cells, and create a microenvironment that facilitates proliferation, growth, and metastases Joyce and Pollard, Nature Reviews Cancer 9: 239 (2009)

6 Acidosis Warburg effect Tumor and proliferative tissue preferentially derive energy through aerobic glycolysis. This leads to the accumulation of lactate which lowers ph. Vander Heiden et al. Science 2009:324 (5930):

7 Acidosis Tumour acidosis gives rise to more difficult treatment, and it increases resistance to chemo- and radio-therapies and is postulated to increase metastases Acidosis Increased radioresistance Resistance to anthracyclines and weakly basic drugs Increased metastases Increased migration and invasion Mutagenesis / clastogenesis Apoptosis Robert A. Gatenby and Robert J. Gillies Nature Reviews Cancer 4:

8 Product Concept By changing the microenvironment, we can potentially treat solid tumours by creating an alkaline microenvironment Alkalinity has potential direct cytotoxic effect on tumours Potential increase in action of other chemo- and radio-therapies Potential reduction of metastatic processes

9 DOS47 Platform Concept DOS47 (urease) an enzyme that can: Reverse Tumour Acidity Apply Natural Metabolic Toxin (Ammonia) Induce Chemo-optimized Environment 3H 2 O Urea 2NH 4 OH + CO 2

10 DOS47 Platform Concept SD antibody (L) Cross-linker DOS47 L-DOS47 Coupled with a protein enzyme that Proprietary Antibody-Protein Conjugates processes urea (found ubiquitously in the (APC) Platform to manipulate the body) into ammonia and CO 2 microenvironment surrounding solid tumours When administered, the conjugate targets specific antigens and creates a basic environment surrounding the tumour through the conversion of urea into ammonia by urease Consists of a targeting antibody that specifically recognizes highly expressed antigens on target tumours

11 DOS47 - Novel Treatment LDOS47 Clinical Candidate of Solid Tumours 11

12 DOS47 Platform Advantages No need to internalize the drug Action is at the tumour surface to manipulate microenvironment Delivers cytotoxic ammonia directly to tumour while changing ph Can use antibodies that have no activity, only need specificity No need to target biologically relevant pathways, only differentially expressed tumour antigens Can confer activity to previously inactive antibodies Mechanism is independent of cell growth cycle or signalling pathway MOA is universal, not pathway dependent With new targeting antibodies, can use same MOA to target different tumour types Potential to have combination effect Basic environment may facilitate uptake of other chemotherapeutics

13 L-DOS47 The First Candidate

14 L-DOS47 First clinical candidate SD antibody (L) Cross-linker DOS47 L-DOS47 L-DOS47 is a conjugate of urease with a proprietary camelid single domain antibody specific for ceacam6 Ceacam6 is a cell surface tumor antigen highly expressed on lung, colon, pancreatic and other cancer cells Exploring this candidate for the treatment of non-squamous, nonsmall cell lung cancer (NSCLC)

15 L-DOS47 Binds Primary and Metastatic human cancer tissues Human lung adenocarcinoma tissue biopsies were sectioned and prepared into slides. Positive binding of L- DOS47 is revealed by brown staining with blue counter stain. Immunopositive staining of L- DOS47 in human lung adenocarcinoma metastasized to lymph node. Positive binding of L- DOS47 is revealed by brown staining with blue counter stain. The black pigment is typical for pulmonary or mediastinal lymph node

16 L-DOS47 Cytotoxic to lung tumour cells L-DOS47 binds specifically to ceacam6 positive lung cells L-DOS47 is cytotoxic to ceacam6 positive lung cells

17 L-DOS47 Distributes to Tumor Preferentially Tumour specific localization Full Body Scan A549 tumour (8 x 7 mm) L-DOS47-Cy5.5 Filtered Scan L-DOS47-Cy5.5 Cy5.5 emission

18 Normalized Fluorescence Intensity L-DOS47 Stays on Tumor Persistently and Retards Growth hrs 24hrs 48hrs 72 hrs %Change in Tumor Volume Vehicle Cisplatin L-DOS47 (35U/kg) L-DOS47 (20U/kg) L-DOS47 (10U/kg) Days 0 Time post injection (hours) Imaging in xenograft tumour model shows specificity for tumour and remain at high concentrations for at least 72 hours L-DOS47 retards tumor growth in lung cancer xenograft model

19 L-DOS47 Enhances Chemo Drugs The cytotoxic effect of weakly basic drugs is directly related to the solution ph (left panel). At an acidic tumour ph (<6.8), the effectiveness of these drugs is significantly reduced. L-DOS47 can dramatically raise the effectiveness of these drugs (e.g. navelbine, right panel). This synergistic effect is directly related to its enzymatic properties of generating ammonia from urea and raising solution ph. Depending on the dosages and available urea, a 2 10 fold drug effect enhancement can be observed

20 L-DOS47 Tested Extensively in Toxicology Studies Tissue Cross Reactivity Studies In vitro cell proliferative and cytokine studies Non-GLP and GLP animal toxicology studies (rat and monkey) examining various doses; monitoring clinical signs, blood chemistry, cytokines, immunogenicity, body weight, organ anatomy. Human starting dose calculated from NOAEL, MABEL and PK considerations. Anticipated effective dose well within theoretical tox ceiling L-DOS47 preclinical pharmacological and toxicological profiles are well established

21 US and Polish regulatory agencies have reviewed the entire pre-clinical and toxicology findings and approved INDs for monotherapy Phase I studies

22 Phase I / II Trial L-DOS47 (POL) Interim Data Review (completed October 2013) Date review included all Cohort 1-3 patients and Cohort 4 patients that had completed at least two cycles of L-DOS47 therapy (12 patients in total) L-DOS47 was well tolerated in the first 4 dosing cohorts Immunogenicity and PK profile consistent with animal model data In the first three dosing cohorts, average number of cycles completed per patient increased with each cohort dose escalation In Cohort 3, one patient completed 6 cycles of L-DOS47 therapy with NO disease progression

23 Phase I / II Trial L-DOS47 (POL) Status Update Eighteen (18) patients have completed at least one treatment cycle Cohort 6 enrolment completed end of January 2014 No dose limiting toxicities reported following completion of the first treatment cycle Cohort 7 enrolment to start following the next Trial Steering Committee Meeting scheduled for February 14 th, 2014 Protocol Amendment planned in anticipation of the requirement of additional dosing cohorts Interim Data Review planned following the completion of the 6 week radiology visit for all Cohort 8 patients

24 Clinical Development Plan for L-DOS47 Development of L-DOS47 to create candidate in NSCLC Expand Poland trial to accelerate enrolment based on early review One new Polish site added in January 2014 Complete Phase I component of Poland Study by mid-2014 Top-line results in summer 2014 followed by Phase I interim report Phase II monotherapy to begin immediately following complete enrollment in Phase I Planning combination therapy studies for NSCLC already underway US IND to be submitted by March 2014 for combination therapy with Carboplatin / pemetrexed in first line patients Canadian IND to be submitted by April 2014 for combination with vinorelbine Expected start of enrollment into these combination studies end Q2- start of Q3 2014, once financed

25 Development Plan Development of L-DOS47 to create multi-indication candidate in cancer Leverage FDA IND approval for development into other indications Expand utility of L-DOS47 in new indications Colon Ductal Breast Plan for Phase I/II trials in other indications to begin when upon completion of Phase II monotherapy in Poland expected in Q2 2015

26 Clinical Development Plan for L-DOS47 Phase I/II Combination (Pem/Carbo) First-line therapy in non-squamous NSCLC Pathway to approval in First-line with most popular combination; Most direct reg. approval and market acceptance Phase I Monotherapy (ongoing) Phase II Monotherapy Second-line therapy in non-squamous NSCLC Pathway to approval as maintenance therapy; back-up pathway and label broadening strategy Phase I/II Combination (Vinorelbine) Second-line non-squamous NSCLC Third-line Breast Cancer Pathway to game-changing first line, potential to 2 nd / 3 rd line label broadening; Provides guidance in breast cancer development path

27 Clinical Development Clinical Development Consultant Prof. Kazimierz Roszkowski-Sliz, M.D., Ph.D : Director and Head of the Clinical Department at the National Tuberculosis and Lung Diseases Research Institute in Warsaw. Consults on lung diseases issues for the Polish Ministry of Health. An expert in the field of lung disease and lung cancers with over 230 published papers. Received his M.D. from the Medical Academy in Warsaw and his Ph.D. from the Postgraduate Medical Center in Warsaw.

28 Protocol Development US Protocol Advisory Board Meeting Dr. Chandra Belani: Deputy Director of the Penn State Hershey Cancer Institute (PSHCI), and Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey Medical Center & College of Medicine. Dr. Leora Horn: Assistant Professor of Medicine (Hematology/Oncology) at Vanderbilt-Ingram Cancer Centre Assistant Director, Educator Development Program Clinical Director, Thoracic Oncology Program

29 Protocol Development CDN Protocol Consultant Dr. Randeep Sangha: a Thoracic Medical Oncologist at the Cross Cancer Institute and an Assistant Professor at the University of Alberta. He is the Director of the Provincial Lung Tumor Group in Alberta. Clinical and research interests are in the treatment of thoracic and hematological malignancies as well as Phase I developmental and molecular therapeutics.

30 Strategic Vendor Partnerships Pharm-Olam (Poland) Contract Research Organization Theradex (US) Contract Research Organization Biologics Consulting Group (US) Regulatory Consultant Fisher Scientific (UK, US) Clinical Supplies Management ProductLife (UK) Drug Safety and Pharmacovigilance Charles River Lab (CDN) Preclinical Lab Services

31 Clinical Development Plan for L-DOS Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Carbo/Pem Combo Therapy trial (US) Expansion Cohort (US) Ph I Monotherapy NSCLC (POL) Ph II Mono NSCLC (POL) Planning New indications (Breast or Colon) Vinorelbine Combo Therapy (CAN) Expansion Cohort (CDN) Topline Readouts Phase I MONO Phase II MONO Phase I Carbo/Pem Phase I Vinorelbine Expansion Carbo/Pem

32 R&D Plan Expansion of Pipeline 5 Compounds in various stages of pre-clinical Target areas: Colon, pancreatic, breast, lung Mechanism of Action similar to lead LDOS-47 Potential for similar safety profile and clinical development pathway Value of pipeline candidates enhanced by potential success of LDOS-47 Complete pre-clinical packages for at least two new candidates by end 2014 Fully characterized in vitro data in place Toxicology and efficacy animal models, clinical supply development to be ready for pre-ind discussions in 2014 Create external alliances during 2014 to create new DOS candidates Identify patent expired or non-active antibodies from biotech/pharma

33 Corporate Goal Create Value by: Clinical validating DOS platform technology through development of L-DOS47 in multiple indications Scientifically validating DOS platform: Internally with new pre-clinical candidates Externally though collaboration with others using near-patentexpiry antibodies or non-active antibodies that can be coupled with DOS technology Creating multiple licensing or acquisition opportunities

34 Summary Helix is a unique investment opportunity Lead candidate in NSCLC with realistic timeframe and opportunity to expand indications for mid term growth Platform technology and 5 new pre-clinical candidates to ensure long term growth Ability to work with others assets to create newly valuable conjugates from inactive or patent-expired antibodies Realistic timeline with ability to report results constantly to build value